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Research Article

通过基因工程脐带间充质干细胞作为细胞载体的局部递送，针对恶性胶质瘤的自杀基因治疗。

卷 19, 期 5, 2019

页: [330 - 341] 页: 12

弟呕挨: 10.2174/1566523219666191028103703

价格: $65

摘要

背景：胶质母细胞瘤（GBM）是一种难以消除的恶性肿瘤，因此迫切需要新的疗法。间充质干细胞（MSC）具有定位受损组织，炎症部位和肿瘤的能力，因此是携带抗肿瘤基因治疗肿瘤的良好候选者。用已经用单纯疱疹病毒胸苷激酶（HSV-TK）基因转导的MSC治疗GBM取得了重大进展，因为在用前药更昔洛韦（GCV）治疗后，MSC可以对肿瘤细胞产生旁观者效应。 目的：在本研究中，我们旨在确定表达HSV-TK的脐带间充质干细胞（MSCTK）联合前药GCV处理是否可以对GBM产生旁观者杀伤作用。 方法与结果：与MSCTK：U87比为1：10、1：100和1：100相比，GCV浓度为2.5μM或250μM，当MSCTK与U87细胞以1：1比例共培养时，产生了25μMGCV更稳定的杀伤效果。与U87细胞共培养的大量MSCTK与MSCTK / GCV系统发挥的更好的旁观者效应相关。我们建立了U87驱动的皮下肿瘤模型和脑颅内肿瘤模型，以评估MSCTK / GCV系统对皮下和颅内肿瘤的效率，发现MSCTK / GCV在两种模型中均有效。 MSCTK与肿瘤细胞的比例在该治疗效果中起关键作用，更高的MSCTK / U87比发挥更好的效果。 结论：该研究表明MSCTK / GCV系统对GBM肿瘤细胞具有较强的旁观者作用，该系统可能是GBM术后治疗的有希望的辅助方法。

关键词: 间充质干细胞，胶质母细胞瘤，HSV-TK，旁观者效应，局部基因治疗，脐带，GCV。

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